The present invention relates to methods and devices for the agglomeration of finely divided powders, e.g., powdered medicaments for inhalation therapy.
Finely divided powders, i.e., powders having a very small particle size, typically less than 5-10 .mu.m, are commonly used in inhalation therapy. In this application, the particle size of the powder is of the utmost importance. The diameter of the particles to be inhaled must be less than 10 .mu.m or the particles will not adequately penetrate the bronchial area of the lungs. It is also very important in inhalation therapy that a precisely controlled dosage be administered. The inhaled route of administration enables the dose to be delivered directly to the airways, and thus allows a very small dosage to be given, minimizing side effects, but also making precise metering of the powder dosage crucial.
Particle size control and precise metering are often made problematic by the flow properties of finely divided powders. Most finely divided powders are light, dusty and fluffy. Further, the van der Waals forces of the particles exceed the force of gravity, causing the particles to be cohesive. This combination of properties makes the powder flow poorly, complicating handling, processing and storage, and making it difficult to meter and dispense a precise dosage of the powder. The particles also tend to adhere to each other during storage and handling, forming agglomerates. Because these agglomerates are made up of a number of primary particles, they typically have diameters in excess of 10 .mu.m. Accordingly, if the agglomerates do not break down into primary particles during inhalation the powder dosage will not properly penetrate the bronchial area. Also, if agglomeration is not controlled, random sized agglomerates may result, making precise metering of the powder difficult.
The flow properties of the powder can be improved by controlled agglomeration of the powder, e.g., by vibration, agitation or rolling of the powder with or without a binder. However, the agglomerates must have sufficiently low internal coherence so that they readily break into primary particles during inhalation in an inhalation device.
Methods of controlled agglomeration-are known in the art. For example, Claussen and Petrow (Journal of Materials Technology, vol 4(3), pp. 148-156 (1973)) describe a method of agglomeration by tumbling in a cylinder tilted at an angle to the horizontal axis of rotation. U.S. Pat. No. 5,143,126 describes a vibratory conveyor for forming flowable agglomerates from previously poorly flowable fine-grained powder by subjecting the powder to a mechanical vibration step prior to transport and metering. GB 1,569,611 describes a process for agglomeration of a drug into soft pellets, using a binder to produce a paste which is extruded through a sieve to create agglomerates. GB 2,187,952 describes a method of agglomeration by kneading a crystalline powder as it is conveyed by conveying screws through an extruder.